Potassium tert-butoxide → 6-chloro-N-(4-methoxybenzyl)-N-(5-methylpyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1943436Notes

Reaction equation

HRID 1943436 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)=[CH:5][CH:4]=1.CC(C)([O-])C.[K+].Br[C:25]1[C:26]2[N:27]([CH:32]=[CH:33][N:34]=2)[N:28]=[C:29]([Cl:31])[CH:30]=1>C1COCC1>[Cl:31][C:29]1[CH:30]=[C:25]([N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[C:26]2[N:27]([CH:32]=[CH:33][N:34]=2)[N:28]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 29543179N-(4-methoxybenzyl)-5-methylpyridin-2-amineHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

Product 1

HCID 596243566-chloro-N-(4-methoxybenzyl)-N-(5-methylpyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineYield 0.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a flask was added N-(4-methoxybenzyl)-5-methylpyridin-2-amine (147 g, 645 mmol) in THF (5 mL) at 25° C. The solution was stirred at 25° C. and potassium t-butoxide (1936 mL, 1936 mmol) was added. The reaction solution was stirred at 25° C. for 30 minutes. Next, 8-bromo-6-chloroimidazo[1,2-b]pyridazine (150 g, 645 mmol, Example 1 from WO 2007/038314) was added and the reaction solution was stirred at room temperature for 1 hour. The reaction was quenched with ethyl acetate and the solvent was removed in vacuo. The residue was redissolved in ethyl acetate, washed with sat NaHCO3, and sat. NaCl and dried (Na2SO4), filt and concentrated in vacuo to give the crude product. The residue was purified via ISCO (5% EtOAC/DCM; 12 g column) to give pure product 6-chloro-N-(4-methoxybenzyl)-N-(5-methylpyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.1367 g, 0.360 mmol, 0.056% yield).

Workup

  1. stirringThe reaction solution was stirred at 25° C. for 30 minutes
  2. stirringthe reaction solution was stirred at room temperature for 1 hour
  3. customThe reaction was quenched with ethyl acetate
  4. customthe solvent was removed in vacuo
  5. dissolutionThe residue was redissolved in ethyl acetate
  6. washwashed
  7. dry with materialdried (Na2SO4)
  8. concentrationfilt and concentrated in vacuo
  9. customto give the crude product
  10. customThe residue was purified via ISCO (5% EtOAC/DCM; 12 g column)

Sources & evidence

ORD record
ord-b20a40f156074b258d7d519349a1f6d2
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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